Previous work has demonstrated that dopamine and estradiol interact in the CNS in the regulation of pituitary gonadotropin secretion. The proposed experiments will attempt to characterize certain aspects of the central interaction of dopamine and estradiol and to elucidate possible mechanisms or subcellular sites of interaction. Effects of selected dopaminergic agonists and antagonists on nuclear estradiol binding in estradiol target area in CNS will be investigated by measuring total uptake and subcellular distribution of specifically bound estradiol in response to the drugs used. The mechanism of the dopaminergic stimulation of nuclear estradiol uptake observed in our laboratory will be investigated by means of time course studies of estradiol nuclear binding. An attempt will also be made to determine the subcellular site of action of drugs affecting estradiol binding by means of studies of nuclear binding of estradiol after nuclear and extranuclear fractions from tissues of animals receiving no pretreatment or treatment with a dopaminergic or antagonist are recombined. Other studies will examine effects of previous endocrine history on the response of estradiol-concentrating neurons to dopaminergic agonists and antagonists in rats in both sexes and in androgen-sterilized female rats, and in rats at different times following gonadectomy.